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dc.contributor.authorCooper, Philip R.
dc.contributor.authorMesaros, A. Clementina
dc.contributor.authorZhang, Jie
dc.contributor.authorChristmas, Peter
dc.contributor.authorStark, Christopher M.
dc.contributor.authorDouaidy, Karim
dc.contributor.authorMittelman, Michael A.
dc.contributor.authorSoberman, Roy Jason
dc.contributor.authorBlair, Ian A.
dc.contributor.authorPanettieri, Reynold A.
dc.date.accessioned2012-02-19T23:35:33Z
dc.date.issued2010
dc.identifier.citationCooper, Philip R., A. Clementina Mesaros, Jie Zhang, Peter Christmas, Christopher M. Stark, Karim Douaidy, Michael A. Mittelman, Roy J. Soberman, Ian A. Blair, and Reynold A. Panettieri. 2010. 20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice. PLoS ONE 5(4): e10235.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8191180
dc.description.abstractBackground Ozone, a pollutant known to induce airway hyper-responsiveness (AHR), increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways.Methodology/Principal Findings Male BALB/c mice were exposed to ozone (3 or 6 ppm) or filtered air (controls) for 2 h. Precision cut lung slices (PCLS; 250 µm thickness) containing an intrapulmonary airway (∼0.01 mm\(^2\) lumen area) were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh). Log EC\(_{50}\) and E\(_{\text{max}}\) values were then calculated by measuring the airway lumen area with respect to baseline. In parallel studies, dexamethasone (2.5 mg/kg), or 1-aminobenzotriazol (ABT) (50 mg/kg) were given intraperitoneal injection to naïve mice 18 h prior to ozone exposure. Indomethacin (10 mg/kg) was administered 2 h prior. Cell counts, cytokine levels and liquid chromatography-mass spectrometry (LC-MS) for lipid analysis were assessed in bronchoalveolar lavage (BAL) fluid from ozone exposed and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed animals, which did not contain an increase in neutrophils or interleukin (IL)-6 levels, increased airway sensitivity following in vitro incubation with a naïve PCLS. In parallel, significant increases in oxidized lipids were also identified using LC-MS with increases of 20-HETE that were decreased following ABT treatment.Conclusions/Significance These data show that ozone acutely induces AHR to CCh independent of inflammation and is insensitive to steroid treatment or cyclooxygenase (COX) inhibition. BAL fluid from ozone exposed mice mimicked the effects of in vivo ozone exposure that were associated with marked increases in oxidized lipids. 20-HETE plays a pivotal role in mediating acute ozone-induced AHR.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0010235en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857875/pdf/en_US
dash.licenseLAA
dc.title20-HETE Mediates Ozone-Induced, Neutrophil-Independent Airway Hyper-Responsiveness in Miceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorSoberman, Roy Jason
dc.date.available2012-02-19T23:35:33Z
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0010235*
dash.contributor.affiliatedChristmas, Peter
dash.contributor.affiliatedSoberman, Roy
dash.contributor.affiliatedZhang, Jie


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